Causes of Multiple Sclerosis: Immune Trigger Theory

MS is an autoimmune disorder—that much is known. But beyond that, theories abound about the true causes of the condition, ranging from vitamin D deficiency to cerebrospinal insufficiency. Some ideas have been debunked, while others are still being investigated.

The most recent theory involves the leakage of a clotting protein across the blood-brain barrier that activates an immune response, resulting in a toxic environment in the brain. Nerve cells are then damaged, leading to symptoms of MS.

What was the study?

A recent study, conducted by researchers from the Gladstone Institute of neurological Disease at the University of California-San Francisco, used advanced imaging to observe the early stages of nerve damage in mice with MS. Traditionally, scientists have used brain scans to provide a "snapshot" of the nerve cell destruction, though the causes had not yet been understood.

In this particular study, the researchers used a high-resolution, real-time imaging technique ("in vivo two-photon microscopy") to observe individual cells in mice that were engineered to mimic the human form of MS. Cells in the brain and spinal cords of the mice were studied.

What did they find?

The investigation of the blood-brain barrier has been at the forefront of MS research for some time, where the barrier allows blood proteins to find their way into the brain. According to the findings, the blood-clotting protein fibrinogen is among those that crosses the barrier, and, upon arrival in the brain, incites a strong immune response in the brain. Microglia, the immune system's first line of defense, attack invaders and create a toxic environment for the invader.

The researchers found that this process is at the root of MS, and that fibrinogen leaking into the brain may be the key to solving the MS mystery.

With this information, the researchers then searched for ways to stop the protein from leaking into the brain. After generic modification of the fibrinogen protein, the scientists found that this preserved nerve cells in the brain by eliminating the adverse immune response.

What does it mean?

If the results of this study can ever be transferred to humans, this could change the way MS develops. To eliminate the means by which nerve cells break down, patients would not face worsening symptoms. Though medications exist to help control symptoms and to modify disease progression, this study may provide insight into the underlying causes of the condition and could lead to stopping the disease at the earliest possible stage.

Though this research may not eliminate MS entirely – How would doctors evaluate whose fibrinogen to modify? –it could open up new options for tracking the disease and treating it.